Response of the Normal Eye to High Dose Radiotherapy

his excellent review analyzes ophthalmologic complications followinghigh-dose irradiation of the orbit and surrounding structuresas a necessary adjunct to the treatment of patients with carcinomasof the head and neck region. It confirms the critical importanceof dose-fraction size in the production of radiation complications,especially in nerve tissue.

Analyzing 157 patients treated with irradiation for primary extracranialtumors at the University of Florida, the authors present datashowing a steeply rising incidence of severe dry eye and associatedcomplications following radiation doses of 45 to 50 Gy using conventionalfractionation with treatment of the entire lacrimal gland apparatus.Interestingly, they describe a lower incidence of this complicationat equivalent total doses when twice-daily fractionation (120cGy per fraction) is used--a phenomenon that also has been describedfor changes in salivary gland function [1].

The authors also discuss the development of corneal ulcerationand symblepharon as a consequence of chronic severe dry-eye syndrome.We have noted, especially in the treatment of orbital and retinalmalignancies of childhood that when irradiation of the globe isnecessary, treatment with the lids open is advantageous in minimizingthese problems. Unless the cornea/conjunctiva itself is at risk,this simple action permits some dose-sparing of the cornea andconjunctiva with enface megavoltage techniques and significantlyreduces severe complications [2].

The authors note a paucity of patients in their data set for orbitalirradiation in the dose range of 45 to 57 Gy. As this is a criticaldose range for the establishment of predictable and accurate dose-responsedata, it might be of interest to survey institutions across thecountry for their experience in the treatment of lymphoma occurringat this location, as many radiation therapists treat these patientsto total doses in this range. Although pediatric rhadomyosarcomapatients also are treated with irradiation in this dose range,use of concurrent chemotherapy, especially with the known radiationsensitizer, dactinomycin (Cosmegan), makes interpretation of thesepediatric data problematic, compared to the adult data presentedby the authors [3].

We have been impressed with the importance of retinal vascularhemorrhage as a component of radiation retinopathy as a long-termcause of visual loss. Although, clearing of hemorrhage-affectedvitreous will usually occur, at least to some extent, vision lossin the affected eye is common following such an event. In a reviewof children treated with more than one course of external-beamirradiation for retinoblastoma, effective vision was lost in morethan 95%, primarily following retinal hemorrhage, despite thepassage of many months to over 1 year between treatment courses.This extremely high rate of complications was no doubt accentuatedby the daily radiation fraction size of > 300 cGy used at thattime for the treatment of these children [4].

Avoiding Dose Inhomogeneities

In many patients receiving orbital/globe/optic nerve irradiation,treatment plans heavily weight the anterior field with respectto other fields (usually wedged laterals). These plans are oftenquite inhomogeneous. Despite use of daily radiation fractionsof 180 to 200 cGy, dose inhomogeneities can be considerable (upto 20% to 25%) and potentially lead to portions of the retina/globereceiving > 240 cGy/d despite the fact that much of the treatmentvolume receives 200 cGy/d or less.

Should this be the case, the radiation therapist should eitherdesign a more homogeneous plan, if possible, or suitably reducethe prescribed daily fraction size because of the critical impactof dose fraction on orbital and ocular complications. Use of three-dimensionalplanning and treatment approaches are therefore critical for thesepatients. and their routine use, when indicated, should lead toa significant reduction in complications. This three-dimensionalapproach also facilitates follow-up evaluation and analysis usinga dose-volume histogram approach, which is essential for in-depthunderstanding of a variety of radiation therapy complications.

The critical importance of fraction size in optic nerve toleranceto irradiation cannot be overemphasized. It is now widely acceptedthat a single 800-cGy fraction of irradiation to the optic nerveor chiasm represents a tolerance dose when stereotactic radiosurgeryapproaches are being considered. This must be kept in mind whencontemplating stereotactic approaches or "boosts" forcertain skull base tumors.

Although almost never seen in a group of treated adults, secondtumors of the orbit occur with some frequency in children, especiallythose with genetic abnormalities such as retinoblastoma. Moreover,as these children commonly survive their malignancy, they maybe at risk for this complication for many decades. Orbital bonydevelopment abnormalities may, of course, also be expected.

Although the sclera appears to be remarkably resistant to irradiation,use of radioactive plaques attached to this structure for thetreatment of retinal tumors, particularly choroid melanoma, necessarilydeliver very large doses of irradiation to retinal vessels inorder to deliver adequate doses to the "apex" of thesetumors (due to the inverse-square law). Over time, most patientslose vision, often due to retinal hemorrhage. Proton-beam therapycan potentially obviate this ophthalmologic problem, and use ofconventional dose-fraction treatment with newer hospital-basedproton-beam units may allow equivalent tumor control while betterpreserving vision.

Summary

Overall, as emphasized in this paper, careful control of radiationfraction size to ocular structures and restriction of treatmentvolumes (especially to the lacrimal apparatus), when possible,are of greatest importance in achieving an optimal balance betweentumor control and functional preservation. Newer techniques ofhyperfractionation and three-dimensional treatment planning andinnovative radiation delivery approaches, combined with carefulattention to restricting lacrimal gland treatment, when possible,will minimize visual complications and maximize functional preservation.As the authors note, although surgical reports do not considerenucleation as a complication of the treatment of these malignancies,visual loss occurs rapidly and totally.

References:

1. Leslie MD, Dische S: The early changes in salivary gland functionduring and after radiotherapy given for head and neck cancer.Radiother Oncol 30(1):26-32, 1994.

2. Cassady JR: Radiation therapy in pediatric oncology: Rhadomyosarcoma,in Cassady JR (ed): Medical Radiology-Diagnostic Imaging and RadiationOncology, pp 281-304. Heidleberg, Springer-Verlag, 1994.

3. Dritschilo A, Weichselbaum R, Cassady JR, et al: The role ofradiation therapy in the treatment of soft tissue sarcomas ofchildhood. Cancer 42:1192-1203, 1978.

4. Cassady JR, Sagerman RH, Tretter P: Radiation therapy in retinoblastoma:An analysis of 230 cases. Radiology 93:405-409, 1969.